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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1996-12-10
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pubmed:abstractText |
Treatment with the phosphatidylinositol 3-kinase inhibitor wortmannin promotes approximately 30% decrease in the steady-state number of cell-surface transferrin receptors. This effect is rapid and dose dependent, with maximal down-regulation elicited with 30 min of treatment and with an IC50 approximately 25 nM wortmannin. Wortmannin-treated cells display an increased endocytic rate constant for transferrin internalization and decreased exocytic rate constants for transferrin recycling. In addition to these effects in vivo, wortmannin is a potent inhibitor (IC50 approximately 15 nM) of a cell-free assay that detects the delivery of endocytosed probes into a common compartment. Inhibition of the in vitro assay involves the inactivation of a membrane-associated factor that can be recruited onto the surface of vesicles from the cytosol. Its effects on the cell-free assay suggest that wortmannin inhibits receptor sorting and/or vesicle budding required for delivery of endocytosed material to "mixing" endosomes. This idea is consistent with morphological changes induced by wortmannin, which include the formation of enlarged transferrin-containing structures and the disruption of the perinuclear endosomal compartment. However, the differential effects of wortmannin, specifically increased transferrin receptor internalization and inhibition of receptor recycling, implicate a role for phosphatidylinositol 3-kinase activity in multiple sorting events in the transferrin receptor's membrane traffic pathway.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-1322797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-14731781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-14731803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-1555237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-1649187,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2153110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2174051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2247081,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2447098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2538480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2681226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-2982885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-3015925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-3402440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-3469657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6204769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6279628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6300098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6300903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6300904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-6327050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7479754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7499348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7566155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7575470,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7607321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7624799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7628435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7642697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7642698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7663021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7721937,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7777504,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7794266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7838144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7877690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7929582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-7989323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8010944,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8156600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8162590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8234286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8257416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8303278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8385367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8868465-8387919
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1059-1524
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
355-67
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8868465-Androstadienes,
pubmed-meshheading:8868465-Down-Regulation,
pubmed-meshheading:8868465-Endocytosis,
pubmed-meshheading:8868465-Endosomes,
pubmed-meshheading:8868465-HeLa Cells,
pubmed-meshheading:8868465-Humans,
pubmed-meshheading:8868465-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:8868465-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:8868465-Receptors, Transferrin,
pubmed-meshheading:8868465-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro.
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pubmed:affiliation |
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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